99726-01-9Relevant academic research and scientific papers
Efficient diastereoselective synthesis of a new class of azanucleosides: 2′-homoazanucleosides
Bouton, Jakob,Van Hecke, Kristof,Van Calenbergh, Serge
, p. 4307 - 4316 (2017/06/30)
Azanucleosides, sugar-modified nucleoside analogues containing a 4′ nitrogen atom, have shown a lot of therapeutic potential, e.g. as anti-cancer and antiviral agents. We report the synthesis of a series of 2’-homoazanucleosides, in which the nucleobase is attached to the 2’-position of the pyrrolidine ring via a methylene linker. A suitable orthogonally protected iminosugar was synthesized by ring closing metathesis and dihydroxylation as key steps and further converted to a series of 8 nucleoside analogues through Mitsunobu reaction with suitably protected nucleobases. The 5′ position of the adenine analogue was then further derivatized with thiols to afford 2 additional compounds. The final compounds were evaluated for biological activity.
Dual Palladium(II)/Tertiary Amine Catalysis for Asymmetric Regioselective Rearrangements of Allylic Carbamates
Bauer, Johannes Moritz,Frey, Wolfgang,Peters, René
supporting information, p. 5767 - 5777 (2016/04/20)
The streamlined catalytic access to enantiopure allylic amines as valuable precursors towards chiral β- and γ-aminoalcohols as well as α- and β-aminoacids is desirable for industrial purposes. In this article an enantioselective method is described that transforms achiral allylic alcohols and N-tosylisocyanate in a single step into highly enantioenriched N-tosyl protected allylic amines via an allylic carbamate intermediate. The latter is likely to undergo a cyclisation-induced [3,3]-rearrangement catalysed by a planar chiral pentaphenylferrocene palladacycle in cooperation with a tertiary amine base. The otherwise often indispensable activation of palladacycle catalysts by a silver salt is not required in the present case and there is also no need for an inert gas atmosphere. To further improve the synthetic value, the rearrangement was used to form dimethylaminosulfonyl-protected allylic amines, which can be deprotected under non-reductive conditions.
Palladium-catalyzed vicinal amino alcohols synthesis from allyl amines by in situ tether formation and carboetherification
Orcel, Ugo,Waser, Jerome
supporting information, p. 5250 - 5254 (2015/04/27)
Vicinal amino alcohols are important structural motifs of bioactive compounds. Reported herein is an efficient method for their synthesis based on the palladium-catalyzed oxy-alkynylation, oxy-arylation, or oxy-vinylation of allylic amines. High regio- and stereoselectivity were ensured through the in situ formation of a hemiaminal tether using the cheap commercially available trifluoroacetaldehyde in its hemiacetal form. The obtained compounds are important building blocks, which can be orthogonally deprotected to give either free alcohols, amines, or terminal alkynes.
Total synthesis and configurational assignment of the marine natural product haliclamide
Pfeiffer, Bernhard,Speck-Gisler, Sandra,Barandun, Luzi,Senft, Ursula,De Groot, Claire,Lehmann, Irene,Ganci, Walter,Gertsch, Juerg,Altmann, Karl-Heinz
, p. 2553 - 2563 (2013/05/22)
The marine natural product haliclamide has been synthesized based on macrocyclization by ring-closing olefin metathesis. Using either enantiomer of two of the four building blocks that were employed to assemble the diene precursor for the metathesis reaction, three non-natural isomers of haliclamide were also prepared. On the basis of the comparison of the 1H and 13C NMR spectra of the individual stereoisomers with literature data for the natural product, the configuration of the previously unassigned stereocenters at C9 and C20 of haliclamide could be determined to be S for both carbons. The absolute configuration of haliclamide thus is 2S, 9S, 14R, 20S. The antiproliferative activity of synthetic haliclamide against several human cancer cell lines was found to be in the high μM range. The compound showed no antifungal or antibiotic activity.
Access to enantiomerically enriched cis-2,3-disubstituted azetidines via diastereoselective hydrozirconation
Pradhan, Tarun K.,Krishnan, K. Syam,Vasse, Jean-Luc,Szymoniak, Jan
supporting information; experimental part, p. 1793 - 1795 (2011/06/19)
An asymmetric variant of the hydrozirconation reaction has been established starting from Boc-protected chiral allylic amines. The resulting diastereoselectively formed N-functionalized organozirconiums can be considered as promising chirons. In this case
Synthesis of l-altro-1-deoxynojirimycin, d-allo-1-deoxynojirimycin, and d-galacto-1-deoxynojirimycin from a single chiral cyanohydrin
Van Den Nieuwendijk, Adrianus M. C. H.,Ruben, Mark,Engelsma, Sander E.,Risseeuw, Martijn D. P.,Van Den Berg, Richard J.B.H.N.,Boot, Rolf G.,Aerts, Johannes M.,Brussee, Johannes,Van Der Marel, Gijs A.,Overkleeft, Herman S.
supporting information; experimental part, p. 3957 - 3959 (2010/11/19)
The chemoenzymatic synthesis of three 1-deoxynojirimycin-type iminosugars is reported. Key steps in the synthetic scheme include a Dibal reduction-transimination-sodium borohydride reduction cascade of reactions on an enantiomerically pure cyanohydrin, itself prepared employing almond hydroxynitrile lyase (paHNL) as the common precursor. Ensuing ring-closing metathesis and Upjohn dihydroxylation afford the target compounds.
Unlocking ylide reactivity in the metal-catalyzed allylic substitution reaction: Stereospecific construction of primary allylic amines with aza-ylides
Evans, P. Andrew,Clizbe, Elizabeth A.
supporting information; experimental part, p. 8722 - 8723 (2009/12/04)
(Chemical Equation Presented) The transition metal catalyzed allylic amination represents a powerful and versatile cross-coupling for the asymmetric construction of stereogenic C-N bonds that are present in secondary metabolites and medicinally important
Iridium-catalyzed synthesis of primary allylic amines from allylic alcohols: Sulfamic acid as ammonia equivalent
Defieber, Christian,Ariger, Martin A.,Moriel, Patricia,Carreira, Erick M.
, p. 3139 - 3143 (2008/03/11)
(Chemical Equation Presented) Two for the price of one: Sulfamic acid serves not only as a nitrogen source but also as an in situ activator of hydroxy groups in the first direct iridium-catalyzed synthesis of primary allylic amines from allylic alcohols (see scheme; cod = cycloocta-1,5-diene). The reaction is catalyzed by a commercially available iridium complex and a phosphoramidite-based bidentate phosphorus-olefin ligand.
Chiral oxime ethers in asymmetric synthesis. O-(1-Phenylbutyl)- benzyloxyacetaldoxime, a versatile reagent for the asymmetric synthesis of protected 1,2-aminoalcohols, α-amino acid derivatives, and 2-hydroxymethyl nitrogen heterocycles including iminosugars
Cooper, Tracey S.,Larigo, Alexander S.,Laurent, Pierre,Moody, Christopher J.,Takle, Andrew K.
, p. 1252 - 1262 (2007/10/03)
Addition of a range of organolithium and Grignard reagents to (E)-O-(1-phenylbutyl)benzyloxyacetaldoxime 1 in the presence of boron trifluoride dietbyl etherate is highly diastereoselective. The resulting hydroxylamines 2 undergo N-O bond cleavage upon treatment with zinc-acetic acid or molybdenum hexacarbonyl to give, after N-protection, protected 1,2-aminoalcohols 3 in high enantiomeric purity. Debenzylation of 3a and 3d gave N-Boc (R)-alaninol and (S)-phenylalaninol respectively. The hydroxylamines 2 also serve as α-amino acid precursors, 2i being converted into N-formyl-(R)-alaninyl-(S)-(4-bromo)phenylalanine ester 7, the N-terminal dipeptide of a natural depsipeptide. The versatility of the 1,2-aminoalcohol derivatives was further illustrated by their conversion into 5-, 6- and 7-membered 2-hydroxymethyl nitrogen heterocycles 15-19 in high enantiomeric excess by a ring-closing metathesis reaction. Further reaction of the dihydropyrrole 15 gave the iminosugar 1,4-dideoxy-1,4-imino-D-ribitol. The Royal Society of Chemistry 2005.
O-(1-phenylbutyl)benzyloxyacetaldoxime, a versatile reagent for the asymmetric synthesis of protected 1,2-aminoalcohols and 2-hydroxymethyl nitrogen heterocycles
Cooper, Tracey S.,Larigo, Alexander S.,Laurent, Pierre,Moody, Christopher J.,Takle, Andrew K.
, p. 1730 - 1732 (2007/10/03)
Addition of organometallic reagents to O-(1-phenylbutyl)benzyloxyacetaldoxime in the presence of boron trifluoride diethyl etherate is highly diastereoselective; the resulting hydroxylamines are readily converted into protected 1,2-aminoalcohols and 2-hydroxymethyl nitrogen heterocycles, including the iminosugar 1,4-dideoxy-1,4-imino-D-ribitol, in high enantiomeric excess.
